Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The development of sepsis and multiple organ failure are important determinants of the outcome in critically ill patients. Hepatosplanchnic hypoperfusion and resulting intestinal and hepatic cell damage have been implicated as central events in the development of sepsis and multiple organ failure. Our aim was to study (1) the relation between intramucosal perfusion and intestinal and hepatic cell damage in an early phase of sepsis and (2) the correlation of these parameters with mortality. ⋯ At intensive care unit admission, nonsurvivors had significantly higher I-FABP and L-FABP values than survivors (I-FABP: 325 vs. 76 pg/mL, P < 0.04; L-FABP: 104 vs. 31 ng/mL, P < 0.04). Patients with abdominal sepsis was especially responsible for high-admission I-FABP and L-FABP levels in nonsurvivors (I-FABP: 405 vs. 85 pg/mL, P < 0.04; L-FABP: 121 vs. 59 ng/mL, P < 0.04). This study shows that splanchnic hypoperfusion correlates with intestinal mucosal damage, and that elevated plasma levels of I-FABP and L-FABP are associated with a poor outcome in critically ill patients with abdominal sepsis.
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Depressed heart rate variability (HRV) in septic patients is known to be associated with poor outcome. However, neither etiology of depression of HRV nor its clinical significance has been clearly determined. Because hypercytokinemia plays an important role in sepsis, we investigated the relationships between depressed HRV and IL-6 blood level. ⋯ These findings indicate that reduction in HRV indices is associated with hypercytokinemia, indicating that the autonomic nervous system and the inflammatory response mediated by the cytokine network affect each other. These results also suggest that depression of HRV is closely related to rapid changes in blood pressure. Thus, heart rate variability indices are associated with both the severity and poor outcome of sepsis.
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Randomized Controlled Trial
Glibenclamide dose response in patients with septic shock: effects on norepinephrine requirements, cardiopulmonary performance, and global oxygen transport.
Adenosine triphosphate-sensitive potassium channels are important regulators of arterial vascular smooth muscle tone and are implicated in the pathophysiology of catecholamine tachyphylaxis in septic shock. The present study was designed as a prospective, randomized, double-blinded, clinical pilot study to determine whether different doses of glibenclamide have any effects on norepinephrine requirements, cardiopulmonary hemodynamics, and global oxygen transport in patients with septic shock. We enrolled 30 patients with septic shock requiring invasive hemodynamic monitoring and norepinephrine infusion of 0.5 microg.kg-1.min-1 or greater to maintain MAP between 65 and 75 mmHg. ⋯ Glibenclamide decreased plasma glucose concentrations in a dose-dependent manner but failed to reduce norepinephrine requirements. None of the doses had any effects on cardiopulmonary hemodynamics, global oxygen transport, gas exchange, or electrolytes. These data suggest that oral glibenclamide in doses from 10 to 30 mg fails to counteract arterial hypotension and thus to reduce norepinephrine requirements in catecholamine-dependent human septic shock.
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Multicenter Study
Daily variation in endotoxin levels is associated with increased organ failure in critically ill patients.
High blood levels of endotoxin on admission to the intensive care unit are predictive of adverse outcomes, including organ failure and death. However, the significance of changes in endotoxin levels over time has not been evaluated. We examined whether dynamic daily changes in endotoxin levels resulted in the development of greater organ dysfunction over time in critically ill patients. ⋯ Endotoxin activity assay variability was found to be independent of infection status (P = 0.52). Daily dynamic variation in endotoxin levels is a marker of increased severity of illness as measured by burden of total organ dysfunction over time. Further studies are warranted to assess the role of daily variation in endotoxin levels in the pathogenesis and potential therapy of organ failure in the critically ill.
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Comparative Study
Continuous versus bolus infusion of terlipressin in ovine endotoxemia.
In patients with sepsis, hemodynamic support is often complicated by a tachyphylaxis against conventional vasopressor agents. Bolus infusion of terlipressin, a vasopressin analog, has been reported to increase mean arterial pressure in patients with catecholamine-resistant septic shock. However, bolus infusion of terlipressin may be associated with severe side effects, including pulmonary vasoconstriction and impairment of oxygen delivery. ⋯ These unwanted side effects were prevented by continuous low-dose infusion of the drug. In conclusion, continuous infusion of terlipressin stabilized hemodynamics and improved myocardial performance in endotoxemic ewes without obvious side effects. Continuous low-dose terlipressin infusion may represent a useful alternative treatment of arterial hypotension related to sepsis and systemic inflammatory response syndrome.